APODoC project
Apomorphine for patients with disorders of consciousness
“Taking care of patients in non-responsive wakefulness, minimally conscious or locked-in syndrome”
A project supported by the Fund Generet – King Baudouin Foundation
Coordinators
Principal Investigator
Principal Investigator
Post-doctoral Researcher
PhD Student
PhD Student
Research Project
The study (ClinicalTrials.gov Identifier: NCT03623828 / EudraCT Identifier 2018-003144-23) investigates the effects of subcutaneously administered apomorphine in brain-injured patients with disorders of consciousness (DOC).
Apomorphine, a dopaminergic agent, has exhibited promising clinical effects in preliminary studies. However, the true efficacy and neural mechanisms of this drug for restoration of consciousness are unknown. This study is designed to confirm previously observed positive clinical responses in these patients (Fridman et al. 2009 & Fridman et al. 2010) and to correlate behavioral improvements with multimodal neuroimaging techniques.
Based on the mesocircuit model (Schiff 2010), this project aims to:
- Determine the efficacy of apomorphine to treat patients with DOC,
- Understand the mechanistic brain processes underlying the effect on consciousness recovery using advanced model-based imaging technology,
- Develop biomarkers predicting responsiveness to treatment,
- Evaluate treatment tolerance and side effects.
Forty-eight DOC patients will be randomized to receive a 30-day regimen of apomorphine or placebo. They will be monitored 30 days before therapy, during treatment and 30 days after treatment, using standardized clinical scales and brain-imaging techniques. Follow-up will be performed up to 2 years after treatment.
This will be the first study to investigate the use of apomorphine for the recovery of consciousness using multimodal assessments and response modeling in a randomized clinical trial (RCT).
Results should help to define clearer guidelines in the treatment of patients with disorders of consciousness and allow a better understanding of how dopamine networks are involved in consciousness and its impairments.
Pilot study is now successfully completed and RCT started in June 2021!
Publications
Conference abstract – 2018
“Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments”
LRD. Sanz, N. Lejeune, A. Thibaut, S. Blandiaux, J. Stender, N. Farber, R. Zafonte, S. Laureys, O. Gosseries
Belgian Brain Congress
Article – 2019
“Treating Disorders of Consciousness With Apomorphine: Protocol for a Double-Blind Randomized Controlled Trial Using Multimodal Assessments”
LRD. Sanz, N. Lejeune, S. Blandiaux, E. Bonin, A. Thibaut, J. Stender, NM Farber, ND Schiff, S. Laureys, O. Gosseries
Frontiers in Neurology
Conference abstract – 2019
“Apomorphine for the Treatment of Chronic Disorders of Consciousness: A Case Report with Multimodal Assessments”
LRD. Sanz, N. Lejeune, S. Blandiaux, E. Bonin, F. Raimondo, R. Panda, H. Cassol, NM. Farber, S. Laureys, O. Gosseries
International Brain Injury Association’s 13th World Congress
Poster – 2019
“Treating chronic disorders of consciousness with apomorphine: preliminary results of a multimodal clinical trial”
LRD. Sanz, N. Lejeune, S. Blandiaux, E. Bonin, F. Raimondo, R. Panda, H. Cassol, A. Camargo, NM. Farber, S. Laureys, O. Gosseries
5th Congress of the European Academy of Neurology
Conference abstract – 2019
“Multimodal improvements after apomorphine treatment for chronic disorders of consciousness: preliminary results”
LRD. Sanz, N. Lejeune, E. Bonin, S. Blandiaux, F. Raimondo, R. Panda, H. Cassol, A. Camargo, NM. Farber, S. Laureys, O. Gosseries
4th Swiss Federation of Clinical Neuro-Societies Congress
Conference abstract – 2021
“Apomorphine therapy for patients with disorders of consciousness: a multimodal open-label study”
LRD. Sanz, N. Lejeune, EAC. Bonin, R. Panda, A. Sala, D. Dikenstein, N. Farber, A. Thibaut, S. Laureys, O. Gosseries.
7th Congress of the European Academy of Neurology
Article – 2021
“Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions”
BL. Edlow, LRD. Sanz, L. Polizzotto, N. Pouratian, JD. Rolston, SB. Snider, A. Thibaut, RD. Stevens, O. Gosseries, the Curing Coma Campaign and its contributing members
Neurocritical Care
Poster – 2021
“Increased brain metabolism and EEG connectivity after apomorphine therapy in patients with chronic disorders of consciousness”
LRD. Sanz, N. Lejeune, EAC. Bonin, R. Panda, A. Sala, D. Dikenstein, N. Farber, A. Thibaut, S. Laureys, O. Gosseries.
Virtual World Congress on Brain Injury
Article – 2021
“Repurposing apomorphine for chronic disorders of consciousness: a multimodal open-label study after apomorphine treatment for chronic disorders of consciousness: preliminary results”
LRD. Sanz, N. Lejeune, E. Szymkowicz, E. Bonin, R. Panda, A. Sala, A. Thibaut, D. Dikenstein, S. Van Goethem, D. Ledoux, N. Farber, J. Stender, RD. Zafonte, ND. Schiff, S. Laureys, O. Gosseries.
In preparation